Our objective is to control basic mechanisms of neuron growth, axonal regeneration and formation of synaptic connections sufficiently to promote effective regeneration in mammalian spinal cord and brain. We are analyzing natural axonal growth in the motor systems of developing monkeys at one extreme, and in simplified neuronal systems exposed to growth-stimulating chemicals in tissue culture at the other. A new type of neuron that can be induced to grow or regenerate an axon at will has been developed, and control of growth of its axon is under study. Mouse chimeras are used to distinguish intrinsic from extrinsic factors controlling neuron survival and growth. Sex hormone receptor studies are giving additional new ideas about possible improvement of regeneration. The detailed formation of connections between neurons and their reorganization after focal injury, especially in central inhibitory systems, is being analyzed by new computer-linked graphics systems that allow acquisition of unique quantitative data virtually for the first time. We believe that a multi-disciplinary attack on fundamental problems of neuron development, axonal growth, chemical signalling mechanisms within and between cells, and specific recognition mechanisms mediated at cell surfaces, will lead in time to effective regeneration of axons in adult mammalian spinal cord and brain.